Cyclin Dependent Kinase Inhibitor 1A (CDKN1A)

The p21 (WAF1) protein binds to and inhibits the activity of cyclin-CDK2 or -CDK4 complexes, and thus functions as a regulator of cell cycle progression at G₁. The expression of this gene is tightly controlled by the tumor suppressor protein p53, through which this protein mediates the p53-dependent cell cycle G₁ phase arrest in response to a variety of stress stimuli.

In addition to growth arrest, p21 can mediate cellular senescence and one of the ways it was discovered was as a senescent cell-derived inhibitor. The p21(WAF1) protein can also interact with proliferating cell nuclear antigen (PCNA), a DNA polymerase accessory factor, and plays a regulatory role in S phase DNA replication and DNA damage repair.